System for verifying accuracy of serially-connected drug modules in a combinatorial drug delivery device

ABSTRACT

In one aspect, a system is provided of verifying the accuracy of a plurality of serially-connected drug modules of a combinatorial drug delivery device, each of the drug modules including a drug reservoir, the system including: a machine-readable code located on each of the drug modules; application software configured to generate an activation code based on the machine-readable codes and the sequence of the machine-readable codes; a flow controller on the drug delivery device which is selectively actuatable to a use state to permit flow of drug from the drug delivery device; and, a control unit on the drug delivery device having a computing processing unit configured to compare the activation code with an authentication code, and, wherein, if the authentication code matches the activation code, the computing processing unit causes actuation of the flow controller to permit flow of the drug from the drug delivery device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a National Stage Application under 35 U.S.C. § 371of PCT Application No. PCT/US2020/056660, filed Oct. 21, 2020, whichclaims the priority benefit of U.S. Provisional Application No.62/932,825, filed Nov. 8, 2019; the contents of which are hereinincorporated by reference in their entireties.

BACKGROUND OF THE INVENTION

Combinatorial drug delivery devices and systems are shown and describedin: U.S. Provisional Patent Appl. No. 62/670,266, filed May 11, 2018;PCT Appl. No. PCT/US2019/031727, filed May 10, 2019; PCT Appl. No.PCT/US2019/031762, filed May 10, 2019; and, PCT Appl. No.PCT/US2019/031791, filed May 10, 2019. All of the aforementioned patentfilings are by the same assignee as herein. As shown in theaforementioned patent filings, drug modules of different liquid drugsmay be provided in various combinations to provide different(individualized) drug combinations. The drug modules may be nested,i.e., connected, in series or in parallel, on a tray or other basestructure. Alternatively, the drug modules may be serially connected(vertically and/or horizontally) directly to one another. U.S.Provisional Patent Appl. No. 62/670,266, PCT Appl. No.PCT/US2019/031727, PCT Appl. No. PCT/US2019/031762, and, PCT Appl. No.PCT/US2019/031791, are incorporated by reference herein in theirrespective entireties.

The serially-connected combinatorial system has the advantage incomparison with the nested designs in that it does not require aseparate tray component to make the fluid connections and is thereforemore efficient in components and, thus, in supply chain.

In the nested system, the tray design can ‘store’ information on thecorrect configuration of the modules through the inherent design andlayout of the tray design. For example, the tray may provide aconfiguration (e.g., mechanical cooperating features, such as “lock andkey” features) that guarantee only the correct drug modules can beinserted into the nests of the tray and that the correct drug modulesare arranged in the correct order. This acts as a safety check inpreparing the drug modules for use. In contrast, the serially-connectedsystem does not have a tray-type element and, thus, lacks the ability tohave a safety check on this basis.

Because tray-based mechanical means of error prevention are not possiblein the serially-connected case, it is desirable to implement other meansof detecting configuration errors in the serially-connected system andhence prevent the occurrence of medication errors.

SUMMARY OF THE INVENTION

In one aspect, the subject invention provides a system of verifying theaccuracy of a plurality of serially-connected drug modules of acombinatorial drug delivery device, each of the drug modules including adrug reservoir for accommodating a liquid drug, the system including: amachine-readable code located on each of the drug modules; applicationsoftware on a user's mobile device, the application software configuredto read the machine-readable codes in a captured digital image of theserially-connected drug modules, the application software configured togenerate an activation code based on the machine-readable codes and thesequence of the machine-readable codes; a transmitter on the user'smobile device configured to transmit the activation code; a flowcontroller on the drug delivery device, the flow controller beingselectively actuatable to a use state to permit flow of the liquid drugfrom the drug delivery device; and, a control unit on the drug deliverydevice having a computing processing unit and a receiver, the computingprocessing unit having an associated memory with an authentication codestored thereon, wherein, the receiver is configured to receive theactivation code transmitted by the transmitter, wherein, the computingprocessing unit is configured to compare the activation code with theauthentication code, and, wherein, if the authentication code matchesthe activation code, the computing processing unit is configured tocause actuation of the flow controller to the use state to permit flowof the liquid drug from the drug delivery device.

In a further aspect, the subject invention provides a system ofverifying the accuracy of a plurality of serially-connected drug modulesof a combinatorial drug delivery device, each of the drug modulesincluding a drug reservoir for accommodating a liquid drug, the systemincluding: a machine-readable code located on each of the drug modules;application software on a user's mobile device, the application softwareconfigured to read the machine-readable codes in a captured digitalimage of the serially-connected drug modules, the application softwareconfigured to generate an activation code based on the machine-readablecodes and the sequence of the machine-readable codes, wherein theapplication software includes an application programming interface tocall a remote server to obtain an authentication code associated withthe drug delivery device, the application software configured to comparethe activation code and the authentication code, wherein, if there is amatch between the authentication code and the activation code, theapplication software generating an approval message; a transmitter onthe user's mobile device configured to transmit the approval message; aflow controller on the drug delivery device, the flow controller beingselectively actuatable to a use state to permit flow of the liquid drugfrom the drug delivery device; and, a control unit on the drug deliverydevice having a computing processing unit and a receiver, wherein, thereceiver is configured to receive the approval message transmitted bythe transmitter, and, wherein, based upon the approval message, thecomputing processing unit is configured to cause actuation of the flowcontroller to the use state to permit flow of the liquid drug from thedrug delivery device.

In a further aspect, the subject invention provides a system ofverifying the accuracy of a plurality of serially-connected drug modulesof a combinatorial drug delivery device, each of the drug modulesincluding a drug reservoir for accommodating a liquid drug, the systemincluding: a drug module machine-readable code located on each of thedrug modules; application software on a user's mobile device, theapplication software configured to read the drug module machine-readablecodes in a captured digital image of the serially-connected drug modulesand to read a secondary machine-readable code representing anauthentication code, the application software configured to generate anactivation code based on the drug module machine-readable codes and thesequence of the drug module machine-readable codes, wherein theapplication software configured to compare the activation code and theauthentication code, wherein, if there is a match between theauthentication code and the activation code, the application softwaregenerating an approval message; a transmitter on the user's mobiledevice configured to transmit the approval message; a flow controller onthe drug delivery device, the flow controller being selectivelyactuatable to a use state to permit flow of the liquid drug from thedrug delivery device; and, a control unit on the drug delivery devicehaving a computing processing unit and a receiver, wherein, the receiveris configured to receive the approval message transmitted by thetransmitter, and, wherein, based upon the approval message, thecomputing processing unit is configured to cause actuation of the flowcontroller to the use state to permit flow of the liquid drug from thedrug delivery device.

In yet a further aspect, the subject invention provides a system ofverifying the accuracy of a plurality of serially-connected drug modulesof a combinatorial drug delivery device, each of the drug modulesincluding a drug reservoir for accommodating a liquid drug, the systemincluding: a machine-readable code located on each of the drug modules;application software on a user's mobile device, the application softwareconfigured to read the machine-readable codes in a captured digitalimage of the serially-connected drug modules, the application softwareconfigured to generate an activation code based on the machine-readablecodes and the sequence of the machine-readable codes; a transmitter onthe user's mobile device configured to transmit the activation code; aremote server having stored thereon an authentication code associatedwith the drug delivery device, the remote server configured to receivethe activation code transmitted by the transmitter, wherein, the remoteserver being configured to compare the activation code and theauthentication code, wherein, if the authentication code matches theactivation code, the remote server being configured to generate anapproval message and to transmit the approval message, wherein, uponreceipt of the approval message, the transmitter on the user's mobiledevice transmits the approval message; a flow controller on the drugdelivery device, the flow controller being selectively actuatable to ause state to permit flow of the liquid drug from the drug deliverydevice; and, a control unit on the drug delivery device having acomputing processing unit and a receiver, wherein, the receiver isconfigured to receive the approval message transmitted by thetransmitter on the user's mobile device, and, wherein, based upon theapproval message, the computing processing unit is configured to causeactuation of the flow controller to the use state to permit flow of theliquid drug from the drug delivery device.

These and other features of the invention will be better understoodthrough a study of the detailed description and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-15 depict various features of a system formed in accordance withthe subject invention.

DETAILED DESCRIPTION OF THE INVENTION

With reference to FIG. 1 , a system 10 is shown useable to verify theaccuracy of a plurality of serially-connected drug modules 12 of acombinatorial drug delivery device 14. Each of the drug modules 12includes a drug reservoir 16 for accommodating a liquid drug 18. Thedrug reservoirs 16 may be defined by portions of the drug modules 12, orbe defined by components, such as vials, inserted into the drug modules12. The combinatorial drug delivery device 14, including any aspectthereof, may be formed in accordance with any of the embodimentsdisclosed in any of U.S. Provisional Patent Appl. No. 62/670,266, PCTAppl. No. PCT/US2019/031727, PCT Appl. No. PCT/US2019/031762, and, PCTAppl. No. PCT/US2019/031791. For illustrative purposes, exemplaryfeatures of the combinatorial drug delivery device 14 are describedherein. As will be recognized by those skilled in the art, the subjectinvention is useable with any of the combinatorial drug deliverydevices, including being useable with any of the elements thereof (e.g.,system 10, drug modules 12, manner of connecting the drug modules 12,flow controller 34, etc.), disclosed in any of the aforementioned patentfilings.

As shown in FIG. 2 , the drug modules 12 are serially-connected so as todefine a single flow path for the drug delivery device 14 through theseries of the drug modules 12, through which the liquid drug 18 of eachof the drug modules 12 may be drawn. As shown in FIG. 2 , inlet andoutlet tubing 20, 22, may be provided for each of the drug modules 12 sothat the liquid drug 18 may be drawn, in succession, from each of thedrug modules 12. As shown in FIG. 3 , the inlet and outlet tubing 20, 22may be formed continuously between the drug reservoirs 16 so thatlengths of tubing are provided serving both as an outlet of one of thedrug reservoirs 16 and an inlet for the next drug reservoir 16. FIG. 2shows six of the drug modules 12 (12A-12F). As will be appreciated bythose skilled in the art, any quantity of the drug modules 12 may beutilized. A vent 13 may be provided at a terminus of the flow path (inthe ultimate drug module).

It is noted that one or more by-pass drug modules 12BY may be needed ina series, to accommodate a place in the series, but to not contain anyliquid drug. As shown in FIG. 2A, the by-pass drug module 12BY may haveby-pass tubing 24 which extends from the inlet to the outlet thereof toallow for flow therethrough without a drug reservoir. Alternatively, asshown in FIG. 3 , the by-pass tubing 24 may be provided in lieu of oneof the drug modules 12 to connect two components of the drug deliverydevice 14, such as two of the drug modules 12 or one of the drug modules12 and the controller housing described below.

The liquid drugs 18 contained in the drug modules 12 may vary in typeand concentration. The liquid drug 18 in some of the modules 12 may be adiluent with no pharmaceutically or biologically active agents. The drugmodules 12 may contain one or more solid components which can bereconstituted with flow of a diluent therein to form a liquid drug. Theability of the serially-connected drug modules 12 to contain variousdrug types and concentrations allows for the drug delivery device 14 tobe a combinatorial drug delivery device 14, providing for the mixing ofvarious liquid drugs. The liquid drugs 18 intended for a particularcombination for a patient is prescribed by a physician. The subjectinvention provides for the confirmation of accuracy of the inclusion ofthe particular drug modules 12 in the drug delivery device 14, as wellas, the sequence of the drug modules 12. The sequence of the drugmodules 14 may be significant, possibly having an impact on the efficacyof the ultimate resulting combination.

The drug delivery device 14 preferably includes a controller housing 26to which the serially-connected drug modules 12 are connected. Theoutlet tubing 22 of the first drug module 12A (being the closest to thecontroller housing 26) is in communication with an inlet 28 formed inthe controller housing 26 into which the liquid drug 18 may flow fromthe drug modules 12. Delivery tubing 30 extends from the inlet 28 toconvey the liquid drug 18 through the controller housing 26 to an outlet32. Tubing or conveyances may be secured to the outlet 32 to direct theliquid drug 18 to a storage device (e.g., an IV bag, injector) or to adrug delivery device connected to a patient (e.g., a butterfly needle).

A flow controller 34 is provided in the controller housing 26 whichselectively regulates flow through the delivery tubing 30. In oneembodiment, the flow controller 34 may include an actuatable source ofnegative pressure 36, such as a pump, provided in the controller housing26 to draw the liquid drug 18 through the inlet 28 and discharge theliquid drug 18 through the outlet 32, via the delivery tubing 30 (whichmay be discontinuous). In a quiescent state, the source of negativepressure 36 generates no negative pressure, thus, not drawing the liquiddrug 18. In a further embodiment, the flow controller 34 may include oneor more adjustable valves 38 provided in the controller housing 26configured to selectively regulate flow through the delivery tubing 30,particularly being configured to be selectively adjusted between openand closed states, such as a ball valve. With the use of the valves 38,a source of negative pressure external to the controller housing 26 maybe utilized which is configured to apply negative pressure to the outlet32 to draw the liquid drug 18 therefrom.

A control unit 40 may be provided in the controller housing 26 whichincludes a computing processing unit (CPU) 42. It is preferred that theflow controller 34 be electrically powered to be controlled by the CPU42. For example, an electrical motor or actuator may be provided havinga switch configured to be controlled by the CPU 42. Actuation of themotor can cause the source of negative pressure 30 to be activated(e.g., the pump to be turned on), whereas, actuation of the actuator cancause adjustment of the valve(s) 38 to an open state (e.g., rotation ofthe valve stem to an open state). The switch may be adjusted to an offposition by the CPU 42 to turn off the motor, or close the valve(s).

It is envisioned that the drug modules 12 will be serially-connected,when ready for use. Thus, assembly of the drug modules 12 is required bya user, or on behalf of a user. As a fail-safe mechanism, as shown inFIG. 4 , to ensure that the drug modules 12 are properly included in thedrug delivery device 14 and in the correct sequence, each of the drugmodules 12, when loaded with liquid drug 18, may have applied thereto amachine-readable code 44 corresponding to the liquid drug 18. Themachine-readable codes 44 are preferably affixed to the drug modules 12with permanence to avoid the separation of the machine-readable codes 44from the drug modules 12 during storage or transportation (e.g.,stickers with strong adhesive, glue, etching, etc.). Themachine-readable codes 44 may be in any format, including bar coding andQR coding. The machine-readable codes 44 are arranged to designate adrug type and, possibly, a drug's concentration or strength. The liquiddrug 18 may be loaded into the drug modules 12 in a manufacturingfacility or in a pharmacy with the machine-readable codes 44 beingaffixed at the same time. Care is needed to apply the correctmachine-readable codes 44 to the drug modules 12.

The specific liquid drugs 18 (type, concentration) will be specified byprescription. The drug modules 12 will be prepared to accommodate thespecified liquid drugs 18—the number of the drug modules 12 to beutilized being at least equal to the number of drug components specifiedby the prescription. The drug modules 12, along with the controllerhousing 26, may be delivered to the user or a location associated withthe user as a kit, for assembly. Instructions will be provided withregards to the assembly of the drug modules 12, including the sequenceof the drug modules 12, e.g., first position (closest to the controllerhousing 26), second position, and so forth.

Once the drug modules 12 are assembled with the controller housing 26 asthe drug delivery device 14, the drug delivery device 14 must be readiedto allow for use. To ready the device, a digital image of the entireseries of the serially-connected drug modules 12, particularly toinclude the machine-readable codes 44 of all of the drug modules 12, iscaptured by a digital camera or a device having a digital camera 46(smart phone, tablet, notebook, cell phone). The digital image may becaptured by the device 46 under the control of a user 45 or throughautomated means, e.g., where a digital camera is arranged in a facilitypreparing the drug delivery device 14.

Preferably, the device 46 includes application software 48 configured toread the machine-readable codes 44 to generate an activation code basedon the contents of the machine-readable codes 44 and the sequencethereof. For example, the device 46 may be a mobile device, e.g., asmartphone, which includes a digital camera, and on which is accessiblethe application software 48. Any graphical user interface (GUI) may beprovided on the device 46 allowing for interfacing with a user. Asappreciated by those skilled in the art, bar code and QR coderecognition and reading software is known in the art and is useable withthe application software 48. The application software 48 may be storedas a set of instructions on a non-transitory memory associated with thedevice 46. All or portions of the application software 48 may reside offof the device 46, callable as needed over a network as described below.

Alternatively, the device 46 may be linkable with a secondary device orcomputer processing unit 47, which may be a remote server, associatedwith the application software 48. Here, the digital image captured bythe device 46 is transmitted to the secondary device or CPU 47 to beread by the application software 48. The device 46 may be linked to thesecondary device or CPU 47 via any network 49 (wired, wirelessly,Internet, local area network (LAN), wide area network (WAN)). Thesecondary device or CPU 47 generates the activation code based onreading the machine-readable codes 44 in the captured image. Thesecondary device or CPU 47 may be associated with a non-transitorymemory 50 on which all or a portion of the application software 48 maybe stored as a set of instructions.

As shown in FIG. 4A, the machine-readable codes 44 of each of the drugmodules 12 may be used to generate a combined alphanumeric data stringCDS, with the individual data strings DS of each of the drug modules 12being assembled together in the order of the drug modules 12 to producethe activation code.

The activation code may be used for comparison against an authenticationcode to determine its accuracy. In one embodiment, the authenticationcode may be stored in a non-transitory memory 41 associated with the CPU42 in the controller housing 26. The application software 48 may beconfigured to cause the generated activation code to be transmitted tothe CPU 42 (e.g., via a transmitter T1 on the device 46 and a receiverR1 on the controller housing 26) with the CPU 42 running a comparison todetermine a match. With a match, the CPU 42 may actuate the flowcontroller 34 to enable the delivery of the liquid drug 18.

The transmitter T1 and the receiver R1 may be each formed to be areceiver and a transmitter. Any wireless network protocol may be usedfor wireless communication including, but not limited to, protocolstaken from a 802.11-compliant network, Bluetooth network, cellulardigital packet data (CDPD) network, high speed circuit switched data(HSCSD) network, packet data cellular (PDC-P) network, general packetradio service (GPRS) network, 1× radio transmission technology (1×RTT)network, IrDA network, multichannel multipoint distribution service(MMDS) network, local multipoint distribution service (LMDS) network,and worldwide interoperability for microwave access (WiMAX) network).

In an alternative embodiment, the application software 48, on the device46, may be configured to call, e.g., over the network 49, the secondarydevice or CPU 47 using an application programming interface (API) toretrieve the authentication code therefrom. Alternatively, the device 46may obtain the authentication code from another source, for example,from a machine-readable code provided with the drug modules 12.Thereafter, the application software 48 may compare, on the device 46,the activation code with the authentication code. With a match, theapplication software 48 may generate an approval message which istransmitted to the CPU 42, e.g., using the transmitter T1. The expectedapproval message may be stored in the memory 41. With a match, the CPU42 may actuate the flow controller 34 to enable the delivery of theliquid drug 18. This embodiment avoids the need for the authenticationcode to be stored in the controller housing 26.

In a further embodiment, the application software 48, on the device 46,may transmit, e.g., over the network 49, the activation code to thesecondary device or CPU 47 for comparison with an authentication code.With a match, the secondary device or CPU 47 transmits, e.g., over thenetwork 49, an approval message to the application software 48, with theapplication software 48, in turn, transmitting an approval message tothe CPU 42, e.g., using the transmitter T1. The expected approvalmessage may be stored in the memory 41. With a match, the CPU 42 mayactuate the flow controller 34 to enable the delivery of the liquid drug18. This embodiment avoids the need for the authentication code to bestored in the controller housing 26.

The flow controller 34 may be provided to have a storage (i.e., non-use)state, e.g., where one or more of the adjustable valves 38 are in closedpositions to not permit flow through the delivery tubing 30 to theoutlet 32. In addition, or alternatively, in the storage state, thesource of negative pressure 36 is in a quiescent state. With a match ofthe activation code and the authentication code, as described above, theCPU 42 may actuate the flow controller 34, thus causing the flowcontroller 34 to enter a use state. With the flow controller 34 in a usestate, delivery of the liquid drug 18 from the drug delivery device 14may be achieved. In particular, the one or more adjustable valves 38 maybe adjusted to open positions to permit flow through the delivery tubing30 to the outlet 32. In addition, the source of negative pressure 36 maybe actuated, or, alternatively, may be placed into an active state,awaiting actuation (e.g., by a switch on the controller housing 26and/or through the application software 48 using the device 46).

As will be appreciated by those skilled in the art, the system 10 allowsfor various functionalities. For example, user accounts may beestablished, e.g., stored in the memory 50 in the form of a database.Access may be granted to the user accounts by various entities,including a prescribing physician P, a dispensing pharmacy Ph, and/ormanufacturing location(s) M which prepare one or more components of thedrug delivery device 14. With the user accounts being accessible overthe network 49, details of a prescription may be viewed and/or updatedas needed. This information may be then used in selecting the liquiddrugs 18 to be used in the drug delivery device 14. The user 45 mayaccess his/her account over the network 49 utilizing the device 46,e.g., as mobile device, relying on the GUI to access details as needed.

With the drug delivery device 14 having the receiver R1 configured toalso be a transmitter, details (time, date, confirmation of completion)of dosing drug by the drug delivery device 14 may be transmitted overthe network 49 to the relevant user accounts. Medical practitioners,such as the prescribing physician P, may access this data to confirmcompliance with a dosing regimen.

The system 10 also allows for provision of medical information of apatient useable to determine a prescription. For example, informationbased on testing of a patient may be uploaded to the user accounts whichmay be relied upon in determining the prescription. Variousphysiological parameters and/or biomarkers may be tested with resultsbeing uploaded. This would allow for a review from remote locations,such as by the prescribing physician P, with subsequent viewing of theprescription by the pharmacy Ph and/or manufacturing facility M forfulfillment of the prescription. A kit of the prepared drug modules 12and the controller housing 26 may be forwarded to point-of-use forassembly by the user or an assistant. It is possible that the kit beforwarded to a facility, such as the pharmacy Ph, doctor's office, etc.,where the kit is assembled for the patient.

With reference to FIGS. 6-15 , a non-limiting example of the processflow of the application software 48 is presented, including GUI'spresentable on the device 46 at different stages of the process. Withreference to FIG. 6 , a useable process flow 100 is depicted startingwith a home page or splash screen 102. The process flow 100 continueswith a package scanning subroutine having a launch screen 104 and animage reader or capture screen 106 (where a camera on the device 46 maybe initiated) to read a machine-readable code on packaging associatedwith a kit of the drug modules 12, pre-assembly. This subroutine allowsfor identifying an authentication code associated with a packaged kit ofthe drug modules 12. This subroutine may time out requiring a return tothe launch screen 104 to allow for re-start.

After the package scanning subroutine has been successfully completed,interstitial screen 108 is provided to prompt the user to indicatecompletion of assembly of the drug modules 12. With the user indicatingcompletion (e.g., by depressing button 110), a drug module scanningsubroutine is launched with an image reader or capture screen 112causing a camera of the device 46 to read or capture allmachine-readable codes, in sequence, of the assembled drug modules 12.The application software 48 is configured to generate an activation codebased on the machine-readable codes, including the content andsequencing thereof. If the activation code is generated, as indicated inthe process flow 100, the scan is considered successful (step 114). Ifthe activation code is not successfully generated, e.g., the scan timedout without proper data capture (as shown by screen 117), the processflow at step 116 returns to the launch screen 104 to repeat the packagescanning subroutine.

The application software 48 compares the generated activation code withthe obtained authentication code to determine if a match is present. Ifso, as indicated at step 118, it is determined that the drug modules 12are proper and in proper sequence. This may launch screen 120 whichincludes a listing of the drugs, dose amounts, and their sequencing.

If no match is present between the activation code and theauthentication code, the basis for lack of match may be determined bythe application software 48 and shown as an error. For example, theapplication software 48 may determine the proper drug modules 12 arepresent, but in an incorrect sequence, as indicated by error message122. Alternatively, the application software 48 may determine that oneor more of the drug modules 12 is incorrect as indicated by errormessage 124. Further, the application software 48 may determine that oneof more of the drug modules 12 is missing, thus providing an incompletesequence, as indicated by error message 126. Re-start is possible withreturn to the launch screen 104.

In one embodiment, any of the combinatorial drug delivery devicesdisclosed herein is able to deliver two or more drugs for the benefit ofthe patient suffering from any of a wide range of diseases orconditions, e.g., cancer, autoimmune disorder, inflammatory disorder,cardiovascular disease or fibrotic disorder. In one embodiment, one ormore of drug modules 12 may contain a single drug. In one embodiment,one or more of drug module 12 may contain two or more co-formulateddrugs. In one embodiment, one or more of drug module 12 may contain adrug in solid form (such as a tablet, capsule, powder, lyophilized,spray dried), which can be reconstituted with flow of a diluent thereinto form a liquid drug.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is an immune checkpointinhibitor. In certain embodiments, the immune checkpoint inhibitor isProgrammed Death-1 (“PD-1”) pathway inhibitor, a cytotoxicT-lymphocyte-associated antigen 4 (“CTLA-4”) antagonist, a LymphocyteActivation Gene-3 (“LAG3”) antagonist, a CD80 antagonist, a CD86antagonist, a T cell immunoglobulin and mucin domain (“Tim-3”)antagonist, a T cell immunoreceptor with Ig and ITIM domains (“TIGIT”)antagonist, a CD20 antagonist, a CD96 antagonist, a Indoleamine2,3-dioxygenase (“IDO1”) antagonist, a stimulator of interferon genes(“STING”) antagonist, a GARP antagonist, a CD40 antagonist, AdenosineA2A receptor (“A2aR”) antagonist, a CEACAM1 (CD66a) antagonist, a CEAantagonist, a CD47 antagonist, a Receptor Related Immunoglobulin DomainContaining Protein (“PVRIG”) antagonist, a tryptophan 2,3-dioxygenase(“TDO”) antagonist, a V-domain Ig suppressor of T cell activation(“VISTA”) antagonist, or a Killer-cell Immunoglobulin-like Receptor(“KIR”) antagonist.

In one embodiment, the PD-1 pathway inhibitor is an anti-PD-1 antibodyor antigen binding fragment thereof. In certain embodiments, theanti-PD-1 antibody is pembrolizumab (KEYTRUDA; MK-3475), pidilizumab(CT-011), nivolumab (OPDIVO; BMS-936558), PDR001, MEDI0680 (AMP-514),TSR-042, REGN2810, JS001, AMP-224 (GSK-2661380), PF-06801591, BGB-A317,BI 754091, or SHR-1210.

In one embodiment, the PD-1 pathway inhibitor is an anti-PD-L1 antibodyor antigen binding fragment thereof. In certain embodiments, theanti-PD-L1 antibody is atezolizumab (TECENTRIQ; RG7446; MPDL3280A;RO5541267), durvalumab (MEDI4736), BMS-936559, avelumab (bavencio),LY3300054, CX-072 (Proclaim-CX-072), FAZ053, KN035, or MDX-1105.

In one embodiment, the PD-1 pathway inhibitor is a small molecule drug.In certain embodiments, the PD-1 pathway inhibitor is CA-170. In anotherembodiment, the PD-1 pathway inhibitor is a cell based therapy. In oneembodiment, the cell based therapy is a MiHA-loaded PD-L1/L2-silenceddendritic cell vaccine. In other embodiments, the cell based therapy isan anti-programmed cell death protein 1 antibody expressing pluripotentkiller T lymphocyte, an autologous PD-1-targeted chimeric switchreceptor-modified T lymphocyte, or a PD-1 knockout autologous Tlymphocyte.

In one embodiment, the PD-1 pathway inhibitor is an anti-PD-L2 antibodyor antigen binding fragment thereof. In another embodiment, theanti-PD-L2 antibody is rHIgM12B7.

In one embodiment, the PD-1 pathway inhibitor is a soluble PD-1polypeptide. In certain embodiments, the soluble PD-1 polypeptide is afusion polypeptide. In some embodiments, the soluble PD-1 polypeptidecomprises a ligand binding fragment of the PD-1 extracellular domain. Inother embodiments, the soluble PD-1 polypeptide comprises a ligandbinding fragment of the PD-1 extracellular domain. In anotherembodiment, the soluble PD-1 polypeptide further comprises an Fc domain.

In one embodiment, the immune checkpoint inhibitor is a CTLA-4antagonist. In certain embodiments, the CTLA-4 antagonist is ananti-CTLA-4 antibody or antigen binding fragment thereof. In someembodiments, the anti-CTLA-4 antibody is ipilimumab (YERVOY),tremelimumab (ticilimumab; CP-675,206), AGEN-1884, or ATOR-1015. In oneembodiment, any of the combinatorial drug delivery devices disclosedherein includes a CTLA-4 antagonist, e.g., ipilimumab (YERVOY), and aPD-1 pathway inhibitor, e.g., nivolumab (OPDIVO) or pembrolizumab(KEYTRUDA).

In one embodiment, the immune checkpoint inhibitor is an antagonist ofLAG3. In certain embodiments, the LAG3 antagonist is an anti-LAG3antibody or antigen binding fragment thereof. In certain embodiments,the anti-LAG3 antibody is relatlimab (BMS-986016), MK-4280 (28G-10),REGN3767, GSK2831781, IMP731 (H5L7BW), BAP050, IMP-701 (LAG-5250),IMP321, TSR-033, LAG525, BI 754111, or FS-118. In one embodiment, any ofthe combinatorial drug delivery devices disclosed herein includes a LAG3antagonist, e.g., relatlimab or MK-4280, and a PD-1 pathway inhibitor,e.g., nivolumab (OPDIVO) or pembrolizumab (KEYTRUDA). In one embodiment,any of the combinatorial drug delivery devices disclosed herein includesa LAG3 antagonist, e.g., relatlimab or MK-4280, and a CTLA-4 antagonist,e.g., ipilimumab (YERVOY). In one embodiment, any of the combinatorialdrug delivery devices disclosed herein includes a LAG3 antagonist, e.g.,relatlimab or MK-4280, a CTLA-4 antagonist, e.g., ipilimumab (YERVOY),and a PD-1 pathway inhibitor, e.g., nivolumab (OPDIVO) or pembrolizumab(KEYTRUDA).

In one embodiment, the immune checkpoint inhibitor is a KIR antagonist.In certain embodiments, the KIR antagonist is an anti-KIR antibody orantigen binding fragment thereof. In some embodiments, the anti-KIRantibody is lirilumab (1-7F9, BMS-986015, IPH 2101) or IPH4102.

In one embodiment, the immune checkpoint inhibitor is TIGIT antagonist.In one embodiment, the TIGIT antagonist is an anti-TIGIT antibody orantigen binding fragment thereof. In certain embodiments, the anti-TIGITantibody is BMS-986207, AB 154, COM902 (CGEN-15137), or OMP-313M32.

In one embodiment, the immune checkpoint inhibitor is Tim-3 antagonist.In certain embodiments, the Tim-3 antagonist is an anti-Tim-3 antibodyor antigen binding fragment thereof. In some embodiments, the anti-Tim-3antibody is TSR-022 or LY3321367.

In one embodiment, the immune checkpoint inhibitor is an IDO1antagonist. In another embodiment, the IDO1 antagonist is indoximod(NLG8189; 1-methyl-D-TRP), epacadostat (INCB-024360, INCB-24360),KHK2455, PF-06840003, navoximod (RG6078, GDC-0919, NLG919), BMS-986205(F001287), or pyrrolidine-2,5-dione derivatives.

In one embodiment, the immune checkpoint inhibitor is a STINGantagonist. In certain embodiments, the STING antagonist is 2′ or3′-mono-fluoro substituted cyclic-di-nucleotides; 2′3′-di-fluorosubstituted mixed linkage 2′,5′-3′,5′ cyclic-di-nucleotides; 2′-fluorosubstituted, bis-3′,5′ cyclic-di-nucleotides; 2′,2″-diF-Rp,Rp,bis-3′,5′cyclic-di-nucleotides; or fluorinated cyclic-di-nucleotides.

In one embodiment, the immune checkpoint inhibitor is CD20 antagonist.In some embodiments, the CD20 antagonist is an anti-CD20 antibody orantigen binding fragment thereof. In one embodiment, the anti-CD20antibody is rituximab (RITUXAN; IDEC-102; IDEC-C2B8), ABP 798,ofatumumab, or obinutuzumab.

In one embodiment, the immune checkpoint inhibitor is CD80 antagonist.In certain embodiments, the CD80 antagonist is an anti-CD80 antibody orantigen binding fragment thereof. In one embodiment, the anti-CD80antibody is galiximab or AV 1142742.

In one embodiment, the immune checkpoint inhibitor is a GARP antagonist.In some embodiments, the GARP antagonist is an anti-GARP antibody orantigen binding fragment thereof. In certain embodiments, the anti-GARPantibody is ARGX-115.

In one embodiment, the immune checkpoint inhibitor is a CD40 antagonist.In certain embodiments, the CD40 antagonist is an anti-CD40 antibody forantigen binding fragment thereof. In some embodiments, the anti-CD40antibody is BMS3h-56, lucatumumab (HCD122 and CHIR-12.12), CHIR-5.9, ordacetuzumab (huS2C6, PRO 64553, RG 3636, SGN 14, SGN-40). In anotherembodiment, the CD40 antagonist is a soluble CD40 ligand (CD40-L). Inone embodiment, the soluble CD40 ligand is a fusion polypeptide. In oneembodiment, the soluble CD40 ligand is a CD40-L/FC2 or a monomericCD40-L.

In one embodiment, the immune checkpoint inhibitor is an A2aRantagonist. In some embodiments, the A2aR antagonist is a smallmolecule. In certain embodiments, the A2aR antagonist is CPI-444,PBF-509, istradefylline (KW-6002), preladenant (SCH420814), tozadenant(SYN115), vipadenant (BIIB014), HTL-1071, ST1535, SCH412348, SCH442416,SCH58261, ZM241385, or AZD4635.

In one embodiment, the immune checkpoint inhibitor is a CEACAM1antagonist. In some embodiments, the CEACAM1 antagonist is ananti-CEACAM1 antibody or antigen binding fragment thereof. In oneembodiment, the anti-CEACAM1 antibody is CM-24 (MK-6018).

In one embodiment, the immune checkpoint inhibitor is a CEA antagonist.In one embodiment, the CEA antagonist is an anti-CEA antibody or antigenbinding fragment thereof. In certain embodiments, the anti-CEA antibodyis cergutuzumab amunaleukin (RG7813, RO-6895882) or RG7802 (RO6958688).

In one embodiment, the immune checkpoint inhibitor is a CD47 antagonist.In some embodiments, the CD47 antagonist is an anti-CD47 antibody orantigen binding fragment thereof. In certain embodiments, the anti-CD47antibody is HuF9-G4, CC-90002, TTI-621, ALX148, NI-1701, NI-1801,SRF231, or Effi-DEM.

In one embodiment, the immune checkpoint inhibitor is a PVRIGantagonist. In certain embodiments, the PVRIG antagonist is ananti-PVRIG antibody or antigen binding fragment thereof. In oneembodiment, the anti-PVRIG antibody is COM701 (CGEN-15029).

In one embodiment, the immune checkpoint inhibitor is a TDO antagonist.In one embodiment, the TDO antagonist is a 4-(indol-3-yl)-pyrazolederivative, a 3-indol substituted derivative, or a3-(indol-3-yl)-pyridine derivative. In another embodiment, the immunecheckpoint inhibitor is a dual IDO and TDO antagonist. In oneembodiment, the dual IDO and TDO antagonist is a small molecule.

In one embodiment, the immune checkpoint inhibitor is a VISTAantagonist. In some embodiments, the VISTA antagonist is CA-170 orJNJ-61610588.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is an immune checkpoint enhanceror stimulator.

In one embodiment, the immune checkpoint enhancer or stimulator is aCD28 agonist, a 4-1BB agonist, an OX40 agonist, a CD27 agonist, a CD80agonist, a CD86 agonist, a CD40 agonist, an ICOS agonist, a CD70agonist, or a GITR agonist.

In one embodiment, the immune checkpoint enhancer or stimulator is anOX40 agonist. In certain embodiments, the OX40 agonist is an anti-OX40antibody or antigen binding fragment thereof. In some embodiments, theanti-OX40 antibody is tavolixizumab (MEDI-0562), pogalizumab (MOXR0916,RG7888), GSK3174998, ATOR-1015, MEDI-6383, MEDI-6469, BMS 986178,PF-04518600, or RG7888 (MOXR0916). In another embodiment, the OX40agonist is a cell based therapy. In certain embodiments, the OX40agonist is a GINAKIT cell (iC9-GD2-CD28-OX40-expressing T lymphocytes).

In one embodiment, the immune checkpoint enhancer or stimulator is aCD40 agonist. In some embodiments, the CD40 agonist is an anti-CD40antibody or antigen binding fragment thereof. In one embodiment, theanti-CD40 antibody is ADC-1013 (JNJ-64457107), RG7876 (RO-7009789),HuCD40-M2, APX005M (EPI-0050), or Chi Lob 7/4. In another embodiment,the CD40 agonist is a soluble CD40 ligand (CD40-L). In one embodiment,the soluble CD40 ligand is a fusion polypeptide. In certain embodiments,the soluble CD40 ligand is a trimeric CD40-L (AVREND®).

In one embodiment, the immune checkpoint enhancer or stimulator is aGITR agonist. In certain embodiments, the GITR agonist is an anti-GITRantibody or antigen binding fragment thereof. In one embodiment, theanti-GITR antibody is BMS-986156, TRX518, GWN323, INCAGN01876, orMEDI1873. In one embodiment, the GITR agonist is a soluble GITR ligand(GITRL). In some embodiments, the soluble GITR ligand is a fusionpolypeptide. In another embodiment, the GITR agonist is a cell basedtherapy. In one embodiment, the cell based therapy is an anti-CTLA4 mAbRNA/GITRL RNA-transfected autologous dendritic cell vaccine or a GITRLRNA-transfected autologous dendritic cell vaccine.

In one embodiment, the immune checkpoint enhancer or stimulator a 4-1BBagonist. In some embodiments, the 4-1BB agonist is an anti-4-1BBantibody or antigen binding fragment thereof. In one embodiment, theanti-4-1BB antibody is urelumab or PF-05082566.

In one embodiment, the immune checkpoint enhancer or stimulator is aCD80 agonist or a CD86 agonist. In some embodiments, the CD80 agonist orthe CD86 agonist is a soluble CD80 or CD86 ligand (CTLA-4). In certainembodiments, the soluble CD80 or CD86 ligand is a fusion polypeptide. Inone embodiment, the CD80 or CD86 ligand is CTLA4-Ig (CTLA4-IgG4m,RG2077, or RG1046) or abatacept (ORENCIA, BMS-188667). In otherembodiments, the CD80 agonist or the CD86 agonist is a cell basedtherapy. In one embodiment, the cell based therapy is MGN1601 (anallogeneic renal cell carcinoma vaccine).

In one embodiment, the immune checkpoint enhancer or stimulator is aCD28 agonist. In some embodiments, the CD28 agonist is an anti-CD28antibody or antigen binding fragment thereof. In certain embodiments,the anti-CD28 antibody is TGN1412.

In one embodiment, the CD28 agonist is a cell based therapy. In certainembodiments, the cell based therapy is JCAR015 (anti-CD19-CD28-zetamodified CAR CD3+ T lymphocyte); CD28CAR/CD137CAR-expressing Tlymphocyte; allogeneic CD4+ memory Th1-like T cell s/microparticle-boundanti-CD3/anti-CD28; anti-CD19/CD28/CD3zeta CAR gammaretroviralvector-transduced autologous T lymphocytes KTE-C19; anti-CEAIgCD28TCR-transduced autologous T lymphocytes; anti-EGFRvIIICAR-transduced allogeneic T lymphocytes; autologousCD123CAR-CD28-CD3zeta-EGFRt-expressing T lymphocytes; autologousCD171-specific CAR-CD28 zeta-4-1-BB-EGFRt-expressing T lymphocytes;autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells;autologous PD-1-targeted chimeric switch receptor-modified T lymphocytes(chimera with CD28); CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enrichedT lymphocytes; CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched Tlymphocytes; CD19CAR-CD28zeta-4-1BB-expressing allogeneic T lymphocytes;CD19CAR-CD3zeta-4-1BB-CD28-expressing autologous T lymphocytes;CD28CAR/CD137CAR-expressing T lymphocytes; CD3/CD28 costimulatedvaccine-primed autologous T lymphocytes; or iC9-GD2-CD28-OX40-expressingT lymphocytes.

In one embodiment, the immune checkpoint enhancer or stimulator is aCD27 agonist. In certain embodiments, the CD27 agonist is an anti-CD27antibody or antigen binding fragment thereof. In one embodiment, theanti-CD27 antibody is varlilumab (CDX-1127).

In one embodiment, the immune checkpoint enhancer or stimulator is aCD70 agonist. In some embodiments, the CD70 agonist is an anti-CD70antibody or antigen binding fragment thereof. In one embodiment, theanti-CD70 antibody is ARGX-110.

In one embodiment, the immune checkpoint enhancer or stimulator is anICOS agonist. In certain embodiments, the ICOS agonist is an anti-ICOSantibody or antigen binding fragment thereof. In some embodiments, theanti-ICOS antibody is BMS986226, MEDI-570, GSK3359609, or JTX-2011. Inother embodiments, the ICOS agonist is a soluble ICOS ligand. In someembodiments, the soluble ICOS ligand is a fusion polypeptide. In oneembodiment, the soluble ICOS ligand is AMG 750.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is an anti-CD73 antibody orantigen binding fragment thereof. In certain embodiments, the anti-CD73antibody is MEDI9447.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is a TLR9 agonist. In oneembodiment, the TLR9 agonist is agatolimod sodium.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is a cytokine. In certainembodiments, the cytokine is a chemokine, an interferon, an interleukin,lymphokine, or a member of the tumor necrosis factor family. In someembodiments, the cytokine is IL-2, IL-15, or interferon-gamma.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is a TGF-β antagonist. In someembodiments, the TGF-β antagonist is fresolimumab (GC-1008); NIS793;IMC-TR1 (LY3022859); ISTH0036; trabedersen (AP 12009); recombinanttransforming growth factor-beta-2; autologous HPV-16/18 E6/E7-specificTGF-beta-resistant T lymphocytes; or TGF-beta-resistant LMP-specificcytotoxic T-lymphocytes.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is an iNOS antagonist. In someembodiments, the iNOS antagonist is N-Acetyle-cysteine (NAC),aminoguanidine, L-nitroarginine methyl ester, orS,S-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea).

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is a SHP-1 antagonist.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is a colony stimulating factor 1receptor (“CSF1R”) antagonist. In certain embodiments, the CSF1Rantagonist is an anti-CSF1R antibody or antigen binding fragmentthereof. In some embodiments, the anti-CSF1R antibody is emactuzumab.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is an agonist of a TNF familymember. In some embodiments, the agonist of the TNF family member isATOR 1016, ABBV-621, or Adalimumab.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is an Interleukin-2 (IL-2), suchas aldesleukin. Preferably, the IL-2 or conjugated IL-2 (e.g.,pegylated) has been modified to selectively activate T-effector cellsover T-regulatory cells (“T-eff IL-2”), such as bempegaldesleukin. Inone embodiment, any of the combinatorial drug delivery devices disclosedherein includes a modified IL-2, such as bempegaldesleukin, whichselectively activates T-effector cells over T-regulatory cells, and aPD-1 pathway inhibitor, e.g., nivolumab (OPDIVO) or pembrolizumab(KEYTRUDA). In one embodiment, any of the combinatorial drug deliverydevices disclosed herein includes a modified IL-2, such asbempegaldesleukin, which selectively activates T-effector cells overT-regulatory cells, and a LAG3 antagonist, e.g., relatlimab or MK-4280.In one embodiment, any of the combinatorial drug delivery devicesdisclosed herein includes a modified IL-2, such as bempegaldesleukin,which selectively activates T-effector cells over T-regulatory cells,and a PD-1 pathway inhibitor, e.g., nivolumab (OPDIVO) or pembrolizumab(KEYTRUDA), and a LAG3 antagonist, e.g., relatlimab or MK-4280. In oneembodiment, any of the combinatorial drug delivery devices disclosedherein includes a modified IL-2, such as bempegaldesleukin, whichselectively activates T-effector cells over T-regulatory cells and aCTLA-4 antagonist, e.g., ipilimumab (YERVOY). In one embodiment, any ofthe combinatorial drug delivery devices disclosed herein includes amodified IL-2, such as bempegaldesleukin, which selectively activatesT-effector cells over T-regulatory cells, a PD-1 pathway inhibitor,e.g., nivolumab (OPDIVO) or pembrolizumab (KEYTRUDA), and a CTLA-4antagonist, e.g., ipilimumab (YERVOY). In one embodiment, any of thecombinatorial drug delivery devices disclosed herein includes a modifiedIL-2, such as bempegaldesleukin, which selectively activates T-effectorcells over T-regulatory cells, a CTLA-4 antagonist, e.g., ipilimumab(YERVOY), and a LAG3 antagonist, e.g., relatlimab or MK-4280. In oneembodiment, any of the combinatorial drug delivery devices disclosedherein includes a modified IL-2, such as bempegaldesleukin, whichselectively activates T-effector cells over T-regulatory cells, a PD-1pathway inhibitor, e.g., nivolumab (OPDIVO) or pembrolizumab (KEYTRUDA),a CTLA-4 antagonist, e.g., ipilimumab (YERVOY), and a LAG3 antagonist,e.g., relatlimab or MK-4280.

In one embodiment, one or more of the drugs of any of the combinatorialdrug delivery devices disclosed herein is a CD160 (NK1) agonist. Incertain embodiments, the CD160 (NK1) agonist is an anti-CD160 antibodyor antigen binding fragment thereof. In one embodiment, the anti-CD160antibody is BY55.

In one embodiment, the one or more of drug module 12 may contain asoluble CTLA-4 polypeptide, which can be useful for treating, forinstance, T-cell mediated autoimmune disorders, such as rheumatoidarthritis, juvenile idiopathic arthritis, psoriatic arthritis,graft-versus-host disease, and transplant rejection. In one embodiment,the soluble CTLA-4 polypeptide is abatacept (ORENCIA), belatacept(NULOJIX), RG2077, or RG-1046. In certain embodiments, one or more drugmodules 12 of a combinatorial drug delivery device as described hereininclude a soluble CTLA-4 polypeptide, e.g., abatacept (ORENCIA) and aBruton's tyrosine kinase inhibitor, e.g., branebrutinib. In certainembodiments, one or more drug modules 12 of a combinatorial drugdelivery device as described herein include a soluble CTLA-4polypeptide, e.g., abatacept (ORENCIA) and a tyrosine kinase-2inhibitor, e.g., BMS-986165. In certain embodiments, one or more drugmodules 12 of a combinatorial drug delivery device as described hereininclude a soluble CTLA-4 polypeptide, e.g., abatacept (ORENCIA) and anInterleukin-2 (IL-2) or “T-reg IL-2”, which selectively activatesT-regulatory cells as opposed to T-effector cells, e.g., BMS-986326 andNKTR-358.

What is claimed is:
 1. A system of verifying the accuracy of a pluralityof serially-connected drug modules of a combinatorial drug deliverydevice, each of the drug modules including a drug reservoir foraccommodating a liquid drug, the system comprising: a machine-readablecode located on each of the drug modules; application software on auser's mobile device, the application software configured to read themachine-readable codes in a captured digital image of theserially-connected drug modules, the application software configured togenerate an activation code based on the machine-readable codes and thesequence of the machine-readable codes; a transmitter on the user'smobile device configured to transmit the activation code; a flowcontroller on the drug delivery device, the flow controller beingselectively actuatable to a use state to permit flow of the liquid drugfrom the drug delivery device; and, a control unit on the drug deliverydevice having a computing processing unit and a receiver, the computingprocessing unit having an associated memory with an authentication codestored thereon, wherein, the receiver is configured to receive theactivation code transmitted by the transmitter, wherein, the computingprocessing unit is configured to compare the activation code with theauthentication code, and, wherein, if the authentication code matchesthe activation code, the computing processing unit is configured tocause actuation of the flow controller to the use state to permit flowof the liquid drug from the drug delivery device.
 2. The system as inclaim 1, wherein the machine-readable code is selected from one or moreof the group consisting of: QR codes and bar codes.
 3. The system as inclaim 1, wherein the application software generates data strings for theserially-connected drug modules based on the respective machine-readablecodes thereof, the generated data strings being assembled together basedon the sequence of the serially-connected drug modules to generate acombined alphanumeric data string as the activation code.
 4. The systemas in claim 3, wherein each of the machine-readable codes represents atype of drug contained in the drug reservoir of the respective drugmodule.
 5. The system as in claim 4, wherein each of themachine-readable codes represents a concentration of the drug containedin the reservoir of the respective drug module.
 6. A system of verifyingthe accuracy of a plurality of serially-connected drug modules of acombinatorial drug delivery device, each of the drug modules including adrug reservoir for accommodating a liquid drug, the system comprising: amachine-readable code located on each of the drug modules; applicationsoftware on a user's mobile device, the application software configuredto read the machine-readable codes in a captured digital image of theserially-connected drug modules, the application software configured togenerate an activation code based on the machine-readable codes and thesequence of the machine-readable codes, wherein the application softwareincludes an application programing interface to call a remote server toobtain an authentication code associated with the drug delivery device,the application software configured to compare the activation code andthe authentication code, wherein, if there is a match between theauthentication code and the activation code, the application softwaregenerating an approval message; a transmitter on the user's mobiledevice configured to transmit the approval message; a flow controller onthe drug delivery device, the flow controller being selectivelyactuatable to a use state to permit flow of the liquid drug from thedrug delivery device; and, a control unit on the drug delivery devicehaving a computing processing unit and a receiver, wherein, the receiveris configured to receive the approval message transmitted by thetransmitter, and, wherein, based upon the approval message, thecomputing processing unit is configured to cause actuation of the flowcontroller to the use state to permit flow of the liquid drug from thedrug delivery device.
 7. The system as in claim 6, wherein themachine-readable code is selected from one or more of the groupconsisting of: QR codes and bar codes.
 8. The system as in claim 6,wherein the application software generates data strings for theserially-connected drug modules based on the respective machine-readablecodes thereof, the generated data strings being assembled together basedon the sequence of the serially-connected drug modules to generate acombined alphanumeric data string as the activation code.
 9. The systemas in claim 8, wherein each of the machine-readable codes represents atype of drug contained in the drug reservoir of the respective drugmodule.
 10. The system as in claim 9, wherein each of themachine-readable codes represents a concentration of the drug containedin the reservoir of the respective drug module.
 11. A system ofverifying the accuracy of a plurality of serially-connected drug modulesof a combinatorial drug delivery device, each of the drug modulesincluding a drug reservoir for accommodating a liquid drug, the systemcomprising: a drug module machine-readable code located on each of thedrug modules; application software on a user's mobile device, theapplication software configured to read the drug module machine-readablecodes in a captured digital image of the serially-connected drug modulesand to read a secondary machine-readable code representing anauthentication code, the application software configured to generate anactivation code based on the drug module machine-readable codes and thesequence of the drug module machine-readable codes, wherein theapplication software configured to compare the activation code and theauthentication code, wherein, if there is a match between theauthentication code and the activation code, the application softwaregenerating an approval message; a transmitter on the user's mobiledevice configured to transmit the approval message; a flow controller onthe drug delivery device, the flow controller being selectivelyactuatable to a use state to permit flow of the liquid drug from thedrug delivery device; and, a control unit on the drug delivery devicehaving a computing processing unit and a receiver, wherein, the receiveris configured to receive the approval message transmitted by thetransmitter, and, wherein, based upon the approval message, thecomputing processing unit is configured to cause actuation of the flowcontroller to the use state to permit flow of the liquid drug from thedrug delivery device.
 12. The system as in claim 11, wherein themachine-readable code and the secondary machine-readable code areselected from one or more of the group consisting of: QR codes and barcodes.
 13. The system as in claim 11, wherein the application softwaregenerates data strings for the serially-connected drug modules based onthe respective machine-readable codes thereof, the generated datastrings being assembled together based on the sequence of theserially-connected drug modules to generate a combined alphanumeric datastring as the activation code.
 14. The system as in claim 13, whereineach of the machine-readable codes represents a type of drug containedin the drug reservoir of the respective drug module.
 15. The system asin claim 14, wherein each of the machine-readable codes represents aconcentration of the drug contained in the reservoir of the respectivedrug module.
 16. A system of verifying the accuracy of a plurality ofserially-connected drug modules of a combinatorial drug delivery device,each of the drug modules including a drug reservoir for accommodating aliquid drug, the system comprising: a machine-readable code located oneach of the drug modules; application software on a user's mobiledevice, the application software configured to read the machine-readablecodes in a captured digital image of the serially-connected drugmodules, the application software configured to generate an activationcode based on the machine-readable codes and the sequence of themachine-readable codes; a transmitter on the user's mobile deviceconfigured to transmit the activation code; a remote server havingstored thereon an authentication code associated with the drug deliverydevice, the remote server configured to receive the activation codetransmitted by the transmitter, wherein, the remote server beingconfigured to compare the activation code and the authentication code,wherein, if the authentication code matches the activation code, theremote server being configured to generate an approval message and totransmit the approval message, wherein, upon receipt of the approvalmessage, the transmitter on the user's mobile device transmits theapproval message; a flow controller on the drug delivery device, theflow controller being selectively actuatable to a use state to permitflow of the liquid drug from the drug delivery device; and, a controlunit on the drug delivery device having a computing processing unit anda receiver, wherein, the receiver is configured to receive the approvalmessage transmitted by the transmitter on the user's mobile device, and,wherein, based upon the approval message, the computing processing unitis configured to cause actuation of the flow controller to the use stateto permit flow of the liquid drug from the drug delivery device.
 17. Thesystem as in claim 16, wherein the machine-readable code is selectedfrom one or more of the group consisting of: QR codes and bar codes. 18.The system as in claim 16, wherein the application software generatesdata strings for the serially-connected drug modules based on therespective machine-readable codes thereof, the generated data stringsbeing assembled together based on the sequence of the serially-connecteddrug modules to generate a combined alphanumeric data string as theactivation code.
 19. The system as in claim 18, wherein each of themachine-readable codes represents a type of drug contained in the drugreservoir of the respective drug module.
 20. The system as in claim 19,wherein each of the machine-readable codes represents a concentration ofthe drug contained in the reservoir of the respective drug module.